Fluorouracil, Gemcitabine, and Radiation Therapy in Treating Patients With Cancer of the Pancreas

Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. It is not yet known which treatment regimen is most effective for pancreatic cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of fluorouracil and gemcitabine plus radiation therapy in treating patients with cancer of the pancreas who have undergone surgery.

Timeline

Start

1998-07

Primary completion

2005-10

Completion

—

Outcome

Missed primary endpoint

paper although this improvement was not statistically significant. PMID 18319412 ↗

paper hazard ratio, 0.82 [95% confidence interval, 0.65-1.03]; P = .09). PMID 18319412 ↗

Publications

• Results Abrams RA, Winter KA, Regine WF, Safran H, Hoffman JP, Lustig R, Konski AA, Benson AB, Macdonald JS, Rich TA, Willett CG. Failure to adhere to protocol specified radiation therapy guidelines was associated with decreased survival in RTOG 9704--a phase III trial of adjuvant chemotherapy and chemoradiotherapy for patients with resected adenocarcinoma of the pancreas. Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):809-16. doi: 10.1016/j.ijrobp.2010.11.039. Epub 2011 Feb 1.
• Results Berger AC, Winter K, Hoffman JP, Regine WF, Abrams RA, Safran H, Freedman GM, Benson AB 3rd, Macdonald J, Willett CG. Five year results of US intergroup/RTOG 9704 with postoperative CA 19-9 </=90 U/mL and comparison to the CONKO-001 trial. Int J Radiat Oncol Biol Phys. 2012 Nov 1;84(3):e291-7. doi: 10.1016/j.ijrobp.2012.04.035. Epub 2012 Jun 9.
• Results Farrell JJ, Bae K, Wong J, Guha C, Dicker AP, Elsaleh H. Cytidine deaminase single-nucleotide polymorphism is predictive of toxicity from gemcitabine in patients with pancreatic cancer: RTOG 9704. Pharmacogenomics J. 2012 Oct;12(5):395-403. doi: 10.1038/tpj.2011.22. Epub 2011 May 31.
• Results Regine WF, Winter KA, Abrams R, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Rich TA, Willett CG. Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the U.S. Intergroup/RTOG 9704 phase III trial. Ann Surg Oncol. 2011 May;18(5):1319-26. doi: 10.1245/s10434-011-1630-6. Epub 2011 Mar 10.
• Results Showalter TN, Winter KA, Berger AC, Regine WF, Abrams RA, Safran H, Hoffman JP, Benson AB, MacDonald JS, Willett CG. The influence of total nodes examined, number of positive nodes, and lymph node ratio on survival after surgical resection and adjuvant chemoradiation for pancreatic cancer: a secondary analysis of RTOG 9704. Int J Radiat Oncol Biol Phys. 2011 Dec 1;81(5):1328-35. doi: 10.1016/j.ijrobp.2010.07.1993. Epub 2010 Oct 8.
• Results Tempero MA, Winter KA, Kim GE, et al.: S100A2 as a prognostic marker in patients receiving adjuvant therapy for pancreatic cancer (PC): A secondary analysis of RTOG 9704. [Abstract] J Clin Oncol 29 (Suppl 15): A-4118, 2011.
• Results Farrell J, Bae K, Guha C, et al.: Correlation of cytidine deaminase single nucleotide polymorphism and toxicity from gemcitabine in patients with pancreatic cancer from RTOG 9704. [Abstract] American Society of Clinical Oncology 2009 Gastrointestinal Cancers Symposium, 15-17 January 2009, San Francisco, CA. A-115, 2009.
• Results Farrell JJ, Elsaleh H, Garcia M, Lai R, Ammar A, Regine WF, Abrams R, Benson AB, Macdonald J, Cass CE, Dicker AP, Mackey JR. Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer. Gastroenterology. 2009 Jan;136(1):187-95. doi: 10.1053/j.gastro.2008.09.067. Epub 2008 Oct 7.
• Results Piperdi B, Ng S, Piperdi M, et al.: Single institutional experience with oral capecitabine (Cap) in adjuvant therapy for pancreatic cancer: Gemcitabine (G) followed by Cap/RT followed by G. [Abstract] American Society of Clinical Oncology 2009 Gastrointestinal Cancers Symposium, 15-17 January 2009, San Francisco, CA. A-229, 2009.
• Results Berger AC, Garcia M Jr, Hoffman JP, Regine WF, Abrams RA, Safran H, Konski A, Benson AB 3rd, MacDonald J, Willett CG. Postresection CA 19-9 predicts overall survival in patients with pancreatic cancer treated with adjuvant chemoradiation: a prospective validation by RTOG 9704. J Clin Oncol. 2008 Dec 20;26(36):5918-22. doi: 10.1200/JCO.2008.18.6288. Epub 2008 Nov 24.
• Results Regine WF, Winter KA, Abrams RA, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Kudrimoti MR, Fromm ML, Haddock MG, Schaefer P, Willett CG, Rich TA. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008 Mar 5;299(9):1019-26. doi: 10.1001/jama.299.9.1019.
• Results Abrams RA, Winter KA, Regine WF, et al.: Correlation of RTOG 9704 (adjuvant therapy (rx) of pancreatic adenocarcinoma (pan ca)) radiation therapy quality assurance scores (RTQASc) with survival (S). [Abstract] J Clin Oncol 25 (Suppl 18): A-4523, 2007.
• Results Berger AC, Winter K, Hoffman J, et al.: Post-resection CA 19-9 predicts overall survival (OS) in patients treated with adjuvant chemoradiation: a secondary endpoint of RTOG 9704. [Abstract] J Clin Oncol 25 (Suppl 18): A-4522, 2007.
• Results Regine WF, Garcia M, Berger AC, et al.: Post-resectional CA 19-9 values >90 are associated with significantly worse survival in patients with pancreatic carcinoma treated with adjuvant therapy on RTOG 9704: implications for current and future trials. [Abstract] Int J Radiat Oncol Biol Phys 69 (3 Suppl): A-137, S78, 2007.
• Results Abrams RA, Winter KA, Regine WF, et al.: RTOG 9704: radiotherapy quality assurance (QA) review and survival. [Abstract] Int J Radiat Oncol Biol Phys 66 (3 Suppl 1): A-39, S22, 2006.
• Results Regine WF, Winter KA, Abrams R, et al.: A phase III intergroup trial (RTOG 97-04) of adjuvant pre and post chemoradiation (CRT) 5-FU vs. gemcitabine (G) for resected pancreatic adenocarcinoma. [Abstract] Int J Radiat Oncol Biol Phys 66 (3 Suppl 1): A-42, S23-4, 2006.
• Results Regine WF, Winter KW, Abrams R, et al.: RTOG 9704 a phase III study of adjuvant pre and post chemoradiation (CRT) 5-FU vs. gemcitabine (G) for resected pancreatic adenocarcinoma. [Abstract] J Clin Oncol 24 (Suppl 18): A-4007, 180s, 2006.
• Reyngold M, Winter KA, Regine WF, Abrams RA, Safran H, Hoffman JP, Mowat RB, Hayes JP, Kessel IL, DiPetrillo T, Narayan S, Chen Y, Ben-Josef E, Delouya G, Suh JH, Meyer J, Haddock MG, Feldman M, Gaur R, Yost K, Peterson RA, Sherr DL, Moughan J, Crane CH. Marital Status and Overall Survival in Patients with Resectable Pancreatic Cancer: Results of an Ancillary Analysis of NRG Oncology/RTOG 9704. Oncologist. 2020 Mar;25(3):e477-e483. doi: 10.1634/theoncologist.2019-0562. Epub 2019 Dec 16.
• Lawrence YR, Moughan J, Magliocco AM, Klimowicz AC, Regine WF, Mowat RB, DiPetrillo TA, Small W Jr, Simko JP, Golan T, Winter KA, Guha C, Crane CH, Dicker AP. Expression of the DNA repair gene MLH1 correlates with survival in patients who have resected pancreatic cancer and have received adjuvant chemoradiation: NRG Oncology RTOG Study 9704. Cancer. 2018 Feb 1;124(3):491-498. doi: 10.1002/cncr.31058. Epub 2017 Oct 20.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Gemcitabine	Small molecule	1000 mg/m2	Intravenous
Subject	fluorouracil	Small molecule	250 mg/m2	Intravenous

Indications